A frameshift mutation in Exon V of the A alpha-chain gene leading to truncated A alpha-chains in the homozygous dysfibrinogen Milano III
An inherited dysfunctional fibrinogen variant, denoted as fibrinogen Milano III, was found in a 13-year-old girl suffering from recurrent venous thrombosis. Plasma of the patient exhibited prolonged thrombin time and Reptilase time. Polymerization of fibrin monomers in the presence and absence of ca...
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| Veröffentlicht in: | The Journal of biological chemistry 1994-12, Vol.269 (52), p.33129-33134 |
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| container_title | The Journal of biological chemistry |
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| creator | Furlan, M Steinmann, C Jungo, M Bögli, C Baudo, F Redaelli, R Fedeli, F Lämmle, B |
| description | An inherited dysfunctional fibrinogen variant, denoted as fibrinogen Milano III, was found in a 13-year-old girl suffering
from recurrent venous thrombosis. Plasma of the patient exhibited prolonged thrombin time and Reptilase time. Polymerization
of fibrin monomers in the presence and absence of calcium ions was strongly impaired. SDS-polyacrylamide gel electrophoresis
of reduced fibrinogen showed normal B beta- and gamma-chains, whereas no normal A alpha-chain was detected in the proposita.
Immunoblot analysis with the monoclonal antibody Y18, detecting an epitope within the stretch of amino acids A alpha 1-51,
revealed an A alpha-chain of about 50 kDa with an intact amino terminus. Immunoblotting with antibodies directed against serum
albumin demonstrated the presence of albumin covalently linked to fibrinogen via a disulfide bridge. The structural defect
of fibrinogen Milano III was determined by sequence analysis of a single-stranded fragment of genomic DNA amplified by polymerase
chain reaction. An insertion of a thymine in the exon V of the A alpha-chain gene after the triplet ATT coding for IleA alpha
451 altered the reading frame and caused premature termination of the protein synthesis (Trp452(TGG)-Ser453(TCC)-Stop454(TGA)).
In both parents, normal and mutant alleles were established, leading to duplication of the sequence pattern after the thymine
insertion site, whereas the proposita is homozygous for the new mutation in the fibrinogen A alpha-chain gene. |
| doi_str_mv | 10.1016/S0021-9258(20)30106-X |
| format | Article |
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from recurrent venous thrombosis. Plasma of the patient exhibited prolonged thrombin time and Reptilase time. Polymerization
of fibrin monomers in the presence and absence of calcium ions was strongly impaired. SDS-polyacrylamide gel electrophoresis
of reduced fibrinogen showed normal B beta- and gamma-chains, whereas no normal A alpha-chain was detected in the proposita.
Immunoblot analysis with the monoclonal antibody Y18, detecting an epitope within the stretch of amino acids A alpha 1-51,
revealed an A alpha-chain of about 50 kDa with an intact amino terminus. Immunoblotting with antibodies directed against serum
albumin demonstrated the presence of albumin covalently linked to fibrinogen via a disulfide bridge. The structural defect
of fibrinogen Milano III was determined by sequence analysis of a single-stranded fragment of genomic DNA amplified by polymerase
chain reaction. An insertion of a thymine in the exon V of the A alpha-chain gene after the triplet ATT coding for IleA alpha
451 altered the reading frame and caused premature termination of the protein synthesis (Trp452(TGG)-Ser453(TCC)-Stop454(TGA)).
In both parents, normal and mutant alleles were established, leading to duplication of the sequence pattern after the thymine
insertion site, whereas the proposita is homozygous for the new mutation in the fibrinogen A alpha-chain gene.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(20)30106-X</identifier><identifier>PMID: 7806542</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>albumin ; Base Sequence ; Blotting, Western ; calcium ; Child ; DNA ; Electrophoresis, Polyacrylamide Gel ; Exons ; Female ; Fibrin - chemistry ; fibrinogen ; Fibrinogens, Abnormal - chemistry ; Fibrinogens, Abnormal - genetics ; Frameshift Mutation ; Homozygote ; Humans ; man ; Milano III ; Molecular Sequence Data ; Oxidation-Reduction ; Peptides - chemistry ; Polymers ; thrombin ; thrombosis</subject><ispartof>The Journal of biological chemistry, 1994-12, Vol.269 (52), p.33129-33134</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-febfddff1554536b0c3f85c81c3c0ae54f7ed51613dcb6348feffed0315ed02a3</citedby><cites>FETCH-LOGICAL-c411t-febfddff1554536b0c3f85c81c3c0ae54f7ed51613dcb6348feffed0315ed02a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7806542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Furlan, M</creatorcontrib><creatorcontrib>Steinmann, C</creatorcontrib><creatorcontrib>Jungo, M</creatorcontrib><creatorcontrib>Bögli, C</creatorcontrib><creatorcontrib>Baudo, F</creatorcontrib><creatorcontrib>Redaelli, R</creatorcontrib><creatorcontrib>Fedeli, F</creatorcontrib><creatorcontrib>Lämmle, B</creatorcontrib><title>A frameshift mutation in Exon V of the A alpha-chain gene leading to truncated A alpha-chains in the homozygous dysfibrinogen Milano III</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>An inherited dysfunctional fibrinogen variant, denoted as fibrinogen Milano III, was found in a 13-year-old girl suffering
from recurrent venous thrombosis. Plasma of the patient exhibited prolonged thrombin time and Reptilase time. Polymerization
of fibrin monomers in the presence and absence of calcium ions was strongly impaired. SDS-polyacrylamide gel electrophoresis
of reduced fibrinogen showed normal B beta- and gamma-chains, whereas no normal A alpha-chain was detected in the proposita.
Immunoblot analysis with the monoclonal antibody Y18, detecting an epitope within the stretch of amino acids A alpha 1-51,
revealed an A alpha-chain of about 50 kDa with an intact amino terminus. Immunoblotting with antibodies directed against serum
albumin demonstrated the presence of albumin covalently linked to fibrinogen via a disulfide bridge. The structural defect
of fibrinogen Milano III was determined by sequence analysis of a single-stranded fragment of genomic DNA amplified by polymerase
chain reaction. An insertion of a thymine in the exon V of the A alpha-chain gene after the triplet ATT coding for IleA alpha
451 altered the reading frame and caused premature termination of the protein synthesis (Trp452(TGG)-Ser453(TCC)-Stop454(TGA)).
In both parents, normal and mutant alleles were established, leading to duplication of the sequence pattern after the thymine
insertion site, whereas the proposita is homozygous for the new mutation in the fibrinogen A alpha-chain gene.</description><subject>albumin</subject><subject>Base Sequence</subject><subject>Blotting, Western</subject><subject>calcium</subject><subject>Child</subject><subject>DNA</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Exons</subject><subject>Female</subject><subject>Fibrin - chemistry</subject><subject>fibrinogen</subject><subject>Fibrinogens, Abnormal - chemistry</subject><subject>Fibrinogens, Abnormal - genetics</subject><subject>Frameshift Mutation</subject><subject>Homozygote</subject><subject>Humans</subject><subject>man</subject><subject>Milano III</subject><subject>Molecular Sequence Data</subject><subject>Oxidation-Reduction</subject><subject>Peptides - chemistry</subject><subject>Polymers</subject><subject>thrombin</subject><subject>thrombosis</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAQxy1EVZbCI1TyASE4pHjij02Oq6rASkU9FNDeLMcZb4ySeIkdleUJeGy83VUlTvjgOfw_ZqQfIZfAroCB-nDPWAlFXcrqXcnecwZMFZtnZAGs4gWXsHlOFk-WF-RljD9YfqKGc3K-rJiSolyQPyvqJjNg7LxLdJiTST6M1I_05lee32lwNHVIV9T0u84UtjNZ2-KItEfT-nFLU6BpmkdrErb_-uKh55DuwhB-77dhjrTdR-ebyY8hl9AvvjdjoOv1-hU5c6aP-Po0L8i3jzdfrz8Xt3ef1ter28IKgFQ4bFzbOgdSCslVwyx3lbQVWG6ZQSncElsJCnhrG8VF5dA5bBkHmf_S8Avy9ti7m8LPGWPSg48W-3wH5vv0UtWsFpX4rxGUUjUIno3yaLRTiHFCp3eTH8y018D0AZV-RKUPHHTJ9CMqvcm5y9OCuRmwfUqd2GT9zVHv_LZ78BPqxgfb4aBLVWtZas6hrPlfGkictw</recordid><startdate>19941230</startdate><enddate>19941230</enddate><creator>Furlan, M</creator><creator>Steinmann, C</creator><creator>Jungo, M</creator><creator>Bögli, C</creator><creator>Baudo, F</creator><creator>Redaelli, R</creator><creator>Fedeli, F</creator><creator>Lämmle, B</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T3</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19941230</creationdate><title>A frameshift mutation in Exon V of the A alpha-chain gene leading to truncated A alpha-chains in the homozygous dysfibrinogen Milano III</title><author>Furlan, M ; Steinmann, C ; Jungo, M ; Bögli, C ; Baudo, F ; Redaelli, R ; Fedeli, F ; Lämmle, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-febfddff1554536b0c3f85c81c3c0ae54f7ed51613dcb6348feffed0315ed02a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>albumin</topic><topic>Base Sequence</topic><topic>Blotting, Western</topic><topic>calcium</topic><topic>Child</topic><topic>DNA</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Exons</topic><topic>Female</topic><topic>Fibrin - chemistry</topic><topic>fibrinogen</topic><topic>Fibrinogens, Abnormal - chemistry</topic><topic>Fibrinogens, Abnormal - genetics</topic><topic>Frameshift Mutation</topic><topic>Homozygote</topic><topic>Humans</topic><topic>man</topic><topic>Milano III</topic><topic>Molecular Sequence Data</topic><topic>Oxidation-Reduction</topic><topic>Peptides - chemistry</topic><topic>Polymers</topic><topic>thrombin</topic><topic>thrombosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Furlan, M</creatorcontrib><creatorcontrib>Steinmann, C</creatorcontrib><creatorcontrib>Jungo, M</creatorcontrib><creatorcontrib>Bögli, C</creatorcontrib><creatorcontrib>Baudo, F</creatorcontrib><creatorcontrib>Redaelli, R</creatorcontrib><creatorcontrib>Fedeli, F</creatorcontrib><creatorcontrib>Lämmle, B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Human Genome Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Furlan, M</au><au>Steinmann, C</au><au>Jungo, M</au><au>Bögli, C</au><au>Baudo, F</au><au>Redaelli, R</au><au>Fedeli, F</au><au>Lämmle, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A frameshift mutation in Exon V of the A alpha-chain gene leading to truncated A alpha-chains in the homozygous dysfibrinogen Milano III</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1994-12-30</date><risdate>1994</risdate><volume>269</volume><issue>52</issue><spage>33129</spage><epage>33134</epage><pages>33129-33134</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>An inherited dysfunctional fibrinogen variant, denoted as fibrinogen Milano III, was found in a 13-year-old girl suffering
from recurrent venous thrombosis. Plasma of the patient exhibited prolonged thrombin time and Reptilase time. Polymerization
of fibrin monomers in the presence and absence of calcium ions was strongly impaired. SDS-polyacrylamide gel electrophoresis
of reduced fibrinogen showed normal B beta- and gamma-chains, whereas no normal A alpha-chain was detected in the proposita.
Immunoblot analysis with the monoclonal antibody Y18, detecting an epitope within the stretch of amino acids A alpha 1-51,
revealed an A alpha-chain of about 50 kDa with an intact amino terminus. Immunoblotting with antibodies directed against serum
albumin demonstrated the presence of albumin covalently linked to fibrinogen via a disulfide bridge. The structural defect
of fibrinogen Milano III was determined by sequence analysis of a single-stranded fragment of genomic DNA amplified by polymerase
chain reaction. An insertion of a thymine in the exon V of the A alpha-chain gene after the triplet ATT coding for IleA alpha
451 altered the reading frame and caused premature termination of the protein synthesis (Trp452(TGG)-Ser453(TCC)-Stop454(TGA)).
In both parents, normal and mutant alleles were established, leading to duplication of the sequence pattern after the thymine
insertion site, whereas the proposita is homozygous for the new mutation in the fibrinogen A alpha-chain gene.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>7806542</pmid><doi>10.1016/S0021-9258(20)30106-X</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | albumin Base Sequence Blotting, Western calcium Child DNA Electrophoresis, Polyacrylamide Gel Exons Female Fibrin - chemistry fibrinogen Fibrinogens, Abnormal - chemistry Fibrinogens, Abnormal - genetics Frameshift Mutation Homozygote Humans man Milano III Molecular Sequence Data Oxidation-Reduction Peptides - chemistry Polymers thrombin thrombosis |
| title | A frameshift mutation in Exon V of the A alpha-chain gene leading to truncated A alpha-chains in the homozygous dysfibrinogen Milano III |
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